The ASCT2 (SLC1A5) and ASCT1 (SLC1A4) transporters are transporters of neutral amino acids such as glutamine and a range of other neutral amino acids in and out of a cell in a Na+ dependent, obligate amino acid exchange process. These transporters, by shuttling of various amino acids across the cell membrane, may facilitate or regulate various physiological processes such as cell growth, proliferation, or even glutamatergic neurotransmission via the glutamate/glutamine cycle.
ASCT2 inhibitors, such as L-γ-glutamyl-p-nitroanilide (GPNA) can be used as pharmacologic research tools to inhibit and investigate ASCT2-mediated amino acid transport and function. Such inhibitors can be used as chemotherapeutic agents alone or in combination with other chemotherapeutic agents to treat various human or mammalian tumors or cancers. These compounds can be used as anti-metabolite agents alone or in combination with other chemotherapeutic agents to slow or prevent growth of various human or mammalian tumors and they can serve as effective anti-microbial agents to suppress growth of various pathogenic microbes. A need remains for additional inhibitors of ASCT transporters that can be used as pharmacologic tools to evaluate the physiologic significance of the ASCT transporter by pharmacologic intervention and thus better understand its role in various biologic pathways.
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